Effect of protein kinase modulators on the regulation of cathepsin B activity in THP-1 human monocytic leukemia cells.
Cathepsin B (CB), a lysosomal cysteine proteinase, is implicated in cancer metastasis and inflammatory tissue injury. We examined the effects of the protein kinase agonists and inhibitors on the regulation of CB activity in THP-1 human monocytic cells by two macrophage activators, lipopolysaccharide (LPS) and interferon- (IFN- ). CB elevation induced by LPS alone or LPS followed by IFN- was blocked by protein kinase C (PKC) inhibitors staurosporine, H-7, phloretin and bisindolylmaleimide, and by cyclic nucleotide-dependent protein kinase inhibitors HA 1004, H-8, H-89 and cAMP-dependent protein kinase (PKA) inhibitor. The CB activity by LPS and IFN- were augmented by diacylglycerol kinase inhibitor. PKC activator, phorbol 12-myristate 13-acetate (PMA) and PKA activator, dibutyryl cAMP could replace LPS in priming the cells for IFN- stimulation but 8-bromo-cGMP did not. These findings suggest that the activation of PKC and PKA appears to be involved at least in part in the induction of CB activity in THP-1 cells.
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Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002401:Cathepsin B / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D007951:Leukemia, Myeloid; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology; D010693:Phloretin / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D019311:Staurosporine / Q000494:pharmacology; D013449:Sulfonamides; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D007211:Indoles; D007546:Isoquinolines; D008070:Lipopolysaccharides; D008301:Maleimides; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D013449:Sulfonamides; D003994:Bucladesine; D007371:Interferon-gamma; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002401:Cathepsin B; D019311:Staurosporine; C070515:bisindolylmaleimide I; C088060:bisindolylmaleimide; D010693:Phloretin